To investigate patients with renal disease and systemic disorders affecting the kidney by clinical, physiologic, and laboratory methods, including study by light microscopy, electron microscopy, and thin- section immunofluorescence microscopy; to examine the natural history of these disorders by careful clinical follow-up, serial study of renal function, and with renal biopsies. To identify the role of immunologic factors in the pathogenesis of renal diseases, and to provide an approach for systematic evaluation for treatment. Particular attention will be paid to systemic lupus erythematosus and lupus nephritis; idiopathic membranous glomerulonephropathy and its variants; focal glomerulonephritis and glomerulosclerosis and their variants; and diabetic nephropathy. Attempts will be made to measure the nature and type of antibody in serum and deposited in the glomeruli, to measure complexes in serum, and to assess the role of lymphocytotoxins. To study the mechanisms whereby plasma proteins pass from blood to urine. A variety of protein chemistry techniques will be used to analyze urine and serum proteins from a limited group of patients, including immunohistochemical methods with 0.5 mu sections cut from frozen-substituted tissue. The passage of proteins, particularly albumin, through the glomerular basement membrane and into the proximal tubular cells will be studied by immunoelectron microscopy, using peroxidase-conjugated antisera, with special attention to lipoid nephrosis; nephrotic syndrome with minimal glomerular changes and focal glomerulosclerosis; membranous glomerulonephropathy; membranoproliferative glomerulonephritis; and diseases with discontinuities (gaps) in the glomerular basement membrane. Proteins passage across the glomerulus will also be examined in animal models. To undertake futher technical development of methods: (a) solid- phase enzyme-linked immunoassay for quantitation of serum antibodies; (b) measurement and chracterization of circulating antigen-antibody complexes.